tbuckley/cabot-search huggingface dataset:
Circular RNA EIF4G3 suppresses gastric cancer progression through inhibition of β-catenin by promoting δ-catenin ubiquitin degradation and upregulating SIK1
Authors: Xueyan Zang, Jiajia Jiang, Jianmei Gu, Yanke Chen, Maoye Wang, Yu Zhang, Min Fu, Hui Shi, Hui Cai, Hui Qian, Wenrong Xu, Xu Zhang
Journal: Molecular Cancer (2022)

Abstract Background Increasing studies suggest that circular RNAs (circRNAs) are critical regulators of cancer development and progression. However, the biological roles and mechanisms of circRNAs in gastric cancer (GC) remain largely unknown. Methods We identified the differentially expressed circRNAs in GC by analyzing Gene Expression Omnibus (GEO) datasets. We explored the biological roles of circRNAs in GC by in vitro functional assays and in vivo animal studies. We performed tagged RNA affinity purification (TRAP), RNA immunoprecipitation (RIP), mass spectrometry (MS), RNA sequencing, luciferase reporter assays, and rescue experiments to investigate the mechanism of circRNAs in GC. Results Downregulated expression of circular RNA EIF4G3 (circEIF4G3; hsa_circ_0007991) was found in GC and was associated with poor clinical outcomes. Overexpression of circEIF4G3 suppressed GC growth and metastasis through the inhibition of β-catenin signaling, whereas knockdown of circEIF4G3 showed the opposite effects. Mechanistic studies revealed that circEIF4G3 bound to δ-catenin protein to promote its TRIM25-mediated ubiquitin degradation and interacted with miR-4449 to upregulate SIK1 expression. Conclusion Our findings uncovered a tumor suppressor function of circEIF4G3 in GC through the regulation of δ-catenin protein stability and miR-4449/SIK1 axis. CircEIF4G3 may act as a promising prognostic biomarker and therapeutic target for GC.
P-242 Colorectal cancer in young adults: Experience of the medical oncology department of Fez
Authors: Y. Elhaitmy, Z. Benbrahim, S. El Anssari, I. Elbadisy, F. Abbass, L. Amaadour, K. Oualla, S. Arifi, K. Elghazi, M. Nawfel
Journal: Annals of Oncology (2022)
Editor's Note: Dasatinib Plus Nutlin-3 Shows Synergistic Antileukemic Activity in Both p53wild-type and p53mutated B Chronic Lymphocytic Leukemias by Inhibiting the Akt Pathway
Authors: Giorgio Zauli, Rebecca Voltan, Raffaella Bosco, Elisabetta Melloni, Sandra Marmiroli, Gian Matteo Rigolin, Antonio Cuneo, Paola Secchiero
Journal: Clinical Cancer Research (2022)

The editors are publishing this note to inform readers of a concern about this article (1). Figures 3A and 4B contain three sets of similar tubulin control panels: the left panels of Fig. 3A MEC-2 tubulin and the P-ERK 1/2 tubulin panels in Fig. 4B; the right panels of Fig. 3A JVM-2 tubulin and the P-p38 tubulin panels in Fig. 4B; and the right panels of Fig. 3A BJAB tubulin and the P-Akt tubulin panels in Fig. 4B.
P-107 Efficacy of 2nd-line ramucirumab (RAM) plus FOLFIRI for RAS wild-type metastatic colorectal cancer (mCRC) by prior regimen: Subgroup analysis of the JACCRO CC-16
Authors: Y. Okita, A. Tsuji, T. Watanabe, H. Satake, M. Goto, H. Yasui, M. Nakamura, T. Sagawa, K. Kataoka, M. Shiozawa, Y. Sunakawa, H. Ota, M. Kotaka, K. Miwa, Y. Kobayashi, H. Okuyama, M. Kochi, T. Masuishi, M. Takeuchi, W. Ichikawa, M. Fujii
Journal: Annals of Oncology (2022)
P-11 Venous thromboembolism in colorectal cancer patients with BRAF mutation
Authors: L. Ortega Morán, D. Pesántez, E. Brozos Vázquez, D. Fernández Garay, M. Lobo de Mena, P. Ribera Fernández, M. Sánchez Cánovas, M. Salgado Fernandez, E. García Pérez, E. Iriarte Moncho, B. Morón García, C. Font, E. Gallardo, J. Pérez Altozano, A. Muñoz Martín
Journal: Annals of Oncology (2022)
Nature‐Derived Okra Gel as Strong Hemostatic Bioadhesive in Human Blood, Liver, and Heart Trauma of Rabbits and Dogs
Authors: Yu Huang, Chaoqiang Fan, Yuqing Liu, Lu Yang, Weichao Hu, Shuang Liu, Tongchuan Wang, Zhenzhen Shu, Bingyun Li, Malcolm Xing, Shiming Yang
Journal: Advanced Healthcare Materials (2022)

Bioadhesive performance can be compromised due to bleeding. Bleeding increases mortality. Adhesives with hemostatic function are of great significance. A sustainable and robust hemostatic bioadhesive from okra is reported. The adhesive strength reaches around three and six-fold higher than commercial fibrin on pigskin and glass, respectively. The okra gel presents high-pressure resistance and great underwater adhesive strength. In human blood experiments, the okra gel can activate platelets, enhance the adhesion of activated platelets, and release coagulation factors XI and XII. By forming a fast gel layer and closely adhering to the wound, it can quickly stop bleeding in the liver and heart of rabbits and dogs. Meanwhile, okra gel can cause platelet activation at the wound site and further strengthen its hemostatic performance. It is biocompatible, biodegradable, and can promote wound healing and shows potential as a sustainable bioadhesive, especially in the scenario of significant hemorrhage.
Reply to Yongbao Wei, Ruochen Zhang, and Le Lin’s Letter to the Editor re: Börje Ljungberg, Laurence Albiges, Yasmin Abu-Ghanem, et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. Eur Urol. 2022;82:e88
Authors: Börje Ljungberg, Jens Bedke, Umberto Capitanio, Axel Bex
Journal: European Urology (2022)
P-195 A cohort of patients (pt) with HER2-positive (HER2+) advanced gastroesophageal cancer (aGEC) treated at our institution after a decade of tailored targeted therapy
Authors: A. Pous Badia, A. Ferrando Díez, C. Hierro Carbó, S. España Fernández, A. Plaja Salarich, L. Notario Rincon, L. Layos Romero, J. Manzano Mozo, A. Font Pous, J. Linares, M. Álvaro Pardo, A. Calsina Berna, M. Sendrós Madroño, A. Hernandez Marfil, M. Riquelme Olivares, R. López Martos, J. Colan Hernández, E. Garsot Savall, M. Caro Gallarín, E. Barluenga Torres, M. Munné, C. Bugés Sánchez
Journal: Annals of Oncology (2022)
P-92 Real-life experience with maintenance chemotherapy plus biologics after the first-line treatment of RAS wild-type metastatic colon cancer (mCRC): A multicenter Onco-Colon Turkey study
Authors: M. Artac, E. Cubukcu, O. Bozkurt, A. Bilici, S. Celik, M. Ozcelik, B. Oven, E. Simsek, C. Geredeli, M. Karaca, T. Cil, H. Harputluoglu, M. Şendur, H. Turk, U. Kefeli, A. Alacacioglu, D. Tural, A. Sakin, N. Karadurmus, D. Çevik, F. Dane, M. Gumus
Journal: Annals of Oncology (2022)
P-170 Exploratory biomarker findings from regorafenib plus toripalimab in patients with refractory metastatic colorectal cancer (REGOTORI study)
Authors: Y. Yao, Y. Jin, M. Wang, T. Hou, Y. Chen, M. He, M. Li, Y. Huang, Z. Wang, Z. Lv, X. Zou, Q. Zhao, F. Wang
Journal: Annals of Oncology (2022)

REGOTORI study is a phase 1b/2 clinical trial for MSI-L/MSS/pMMR refractory metastatic colorectal cancer (mCRC). Our group previously reported that regorafenib plus toripalimab as later line therapy can improve efficacy and survival of refractory mCRC patients (REGOTORI study). In this study, we did exploratory research on tumor and plasma samples to provide potential biomarkers that may affect the efficacy and survival of combination therapy. Forty-two patients with MSI-L/MSS/pMMR refractory mCRC were enrolled in the REGOTORI study. Before treatment, FFPE tumor tissue samples from patients were subjected to whole-exome sequencing (WES), 520 genes panel and multiplex immunohistochemistry (mIHC) testing, respectively. Before treatment and every evaluation point, peripheral blood samples from patients were examined by 520 genes panel. Somatic mutations, tumor mutation burden (TMB), blood-based intratumor heterogeneity (bITH), high allele frequency blood-based tumor mutation burden (HAF-bTMB) and high allele frequency blood-based intratumor heterogeneity (HAF-bITH) were evaluated accordingly. Overall survival (OS) was significantly worse in patients with higher bITH (p = 0.008), circulating tumor DNA (ctDNA) max AF (p = 0.014), HAF-bTMB (p = 0.032) and HAF-bITH (p = 0.014). Besides, dynamic change of ctDNA concentration seems related to the response of combination treatment. In addition, patients with SMAD4 mutation had no response in combination therapy (0/6) and had worse progressive-free survival (PFS) (p < 0.001) and OS (p = 0.011) than those with SMAD4 wild type; patients with PIK3CA mutation had worse OS (p = 0.01). Further, mIHC show that patients had longer PFS with higher stroma rate of CD3+ (p = 0.007), CD3+ CD8+ (p = 0.016), CD3+ CD8- (p = 0.007) and PD1+ CD3+ (p = 0.007). However, we found WES-TMB was not related to PFS (p = 0.718) or OS (p = 0.647) in this cohort. These results suggest that selective markers of tumor microenvironment could be predictive biomarkers in refractory mCRC patients who received the combination treatment of regorafenib and toriplalimab. Besides, somatic mutation in SMAD4/PIK3CA and the level of bITH, HAF-bITH, ctDNA max AF and HAF-bTMB could be prognostic factors of these patients. Further analyses are needed for larger treatment cohorts.
P-17 Real-life use and long-term effectiveness results from CIREL – the multi-centre, observational study on irinotecan-eluting transarterial chemoembolization in CRLM
Authors: J. Taieb, D. Arnold, H. Prenen, B. Sangro, S. Pernot, B. Zeka, N. Kaufmann, A. Gjoreski, R. Iezzi, P. Pereira
Journal: Annals of Oncology (2022)
SO-24 Young age as bad prognosis of colorectal cancer: An earlier screening needed?
Authors: G. Calderillo-Ruiz, E. Ruiz-Garcia, C. Diaz, M. Herrera, B. Carbajal-López, A. Albarran, M. García-Gámez, E. Perez Yepez
Journal: Annals of Oncology (2022)
Reducing antibiotic use in uncomplicated urinary tract infections in adult women: a systematic review and individual participant data meta-analysis
Authors: Yvonne Kaußner, Christian Röver, Judith Heinz, Eva Hummers, Thomas P.A. Debray, Alastair D. Hay, Stefan Heytens, Ingvild Vik, Paul Little, Michael Moore, Beth Stuart, Florian Wagenlehner, Andreas Kronenberg, Sven Ferry, Tor Monsen, Morten Lindbæk, Tim Friede, Ildikó Gágyor
Journal: Clinical Microbiology and Infection (2022)

BackgroundRandomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics, and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI).ObjectivesTo estimate the effect of these strategies and to identify symptoms, signs, or other factors that indicate a benefit from these strategies.Data sourcesMEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials.Study eligibility criteria, participants and interventionsRCTs investigating any strategies to reduce antibiotics vs. immediate antibiotics in adult women with uUTI in primary care.MethodsWe extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD.ResultsWe analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (OR 3.0; 95% credible interval (CrI), 1.7–5.5; Bayesian p-value (pB) = 0.0017; τ = 0.6), subsequent antibiotic treatment (OR 3.5; 95% CrI, 2.1–5.8; pB = 0.0003) and pyelonephritis (OR 5.6; 95% CrI, 2.3–13.9; pB = 0.0003). Conversely, they decreased overall antibiotic use by 63%.Patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CrI, 2.1–10.8; pB = 0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CrI, 0.3–2.0; pB = 0.667). In patients treated using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis.ConclusionsCompared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing.
P-163 Tyrosine kinase inhibitors (TKIs) plus transarterial chemoembolization (TACE) compared to TACE alone as downstaging therapy in transplant recipients with hepatocellular carcinoma
Authors: A. Esmail, S. Kodali, E. Graviss, D. Nguyen, L. Moore, A. Saharia, A. Uosef, D. Victor, M. Abdelrahim
Journal: Annals of Oncology (2022)
Structures of VWF tubules before and after concatemerization reveal a mechanism of disulfide bond exchange
Authors: Jacob R. Anderson, Jing Li, Timothy A. Springer, Alan Brown
Journal: Blood (2022)

von Willebrand factor (VWF) is an adhesive glycoprotein that circulates in the blood as disulfide-linked concatemers and functions in primary hemostasis. The loss of long VWF concatemers is associated with the excessive bleeding of type 2A von Willebrand disease (VWD). Formation of the disulfide bonds that concatemerize VWF requires VWF to self-associate into helical tubules, yet how the helical tubules template intermolecular disulfide bonds is not known. Here, we report electron cryomicroscopy (cryo-EM) structures of VWF tubules before and after intermolecular disulfide bond formation. The structures provide evidence that VWF tubulates through a charge-neutralization mechanism and that the A1 domain enhances tubule length by crosslinking successive helical turns. In addition, the structures reveal disulfide states before and after disulfide bond-mediated concatemerization. The structures and proposed assembly mechanism provide a foundation to rationalize VWD-causing mutations.
When I use a word . . . . Values
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

The word “values” has many meanings, including “the principles or moral standards held by a person or social group or the generally accepted or personally held judgment of what is valuable and important in life” (<i>OED</i>). Interviewers sometimes ask job interviewees to name the three attributes that they consider most closely reflect their values. Those who advise interviewees often suggest that they choose three items that complement each other, such as “diligent, loyal, reliable” or “honest, ethical, conscientious.” Given the difficulty in choosing just three attributes from long lists and the impossibility of accurately judging the quality of interviewees from their choices, I suggest a different approach: ask the interviewee for their opinion of a set of suggested attributes, positive or negative. Possible combinations might include “arrogant, disdainful, imperious” and “capricious, injudicious, meretricious.” UK NHS trusts are also fond of compiling and publishing lists of their organisational values, assuming that they benefit staff and the way they perform. However, a recent linguistic analysis of the organisational values of 221 NHS trusts showed that the terms “care,” “value respect,” “aspirational,” and “people” all significantly predicted increased sickness absence, while the terms “supportive” and “openness” predicted negative responses from staff. The authors concluded that “these findings should give NHS managers pause for thought, challenging them to reconsider their reliance on value-defining initiatives, and to seek evidence that a focus on values has measurable benefits on outcomes.” In short, they exhorted them, by implication, to stop advertising their organisational values.
P-29 Overall survival and treatment patterns in patients with metastatic colorectal cancer (CRC): A retrospective chart review
Authors: D. Sugrue, J. Gordon, A. Nassar, S. Hartridge-Lambert, H. Kayhanian, A. Ryan, N. Joharatnam-Hogan, M. Rodriguez-Justo, K. Shiu
Journal: Annals of Oncology (2022)
Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial
Authors: J.S. Frenel, J.W. Kim, N. Aryal, R. Asher, D. Berton, L. Vidal, P. Pautier, J.A. Ledermann, R.T. Penson, A.M. Oza, J. Korach, T. Huzarski, S. Pignata, N. Colombo, T.W. Park-Simon, K. Tamura, G.S. Sonke, A.E. Freimund, C.K. Lee, E. Pujade-Lauraine
Journal: Annals of Oncology (2022)
Covid-19: Brazil is recording a fifth of all deaths of under 5s
Authors: Luke Taylor
Journal: BMJ (2022)

Covid-19: Brazil is recording a fifth of all deaths of under 5s Luke TaylorCovid-19 is killing on average two children under the age of 5 years each day in Brazil, a study by the children's health observatory Observa Infância has found.1The number of fatalities in the country equates to around one in every five deaths among under 5s worldwide.Observa Infância researchers Cristiano and Patricia Boccolini studied data from Brazil's national mortality information system and found that 599 children under 5 died from covid-19 in 2020.
SO-38 Clinical efficacy and single-cell analysis of combined BRAF, MEK, and PD-1 inhibition in BRAFV600E colorectal cancer patients
Authors: R. Corcoran, J. Tian, J. Chen, S. Chao, K. Pelka, I. Baiev, P. Sindurakar, J. Allen, J. Meyerhardt, A. Enzinger, P. Enzinger, N. McCleary, S. Klempner, M. Yurgelun, T. Abrams, J. Clark, D. Ryan, M. Giannakis, A. Parikh, N. Hacohen
Journal: Annals of Oncology (2022)
O-4 Trifluridine/tipiracil (TAS-102) with or without bevacizumab in patients with pretreated metastatic esophago-gastric adenocarcinoma (mEGA): A Danish randomized trial (LonGas)
Authors: P. Pfeiffer, M. Yilmaz, M. Nordsmark, S. Möller, I. Elle, M. Ladekarl, S. Winther, C. Qvortrup, L. Baeksgaard
Journal: Annals of Oncology (2022)
Bone morphogenetic protein 4 inhibits pulmonary fibrosis by modulating cellular senescence and mitophagy in lung fibroblasts
Authors: Ruijuan Guan, Liang Yuan, Jingpei Li, Jian Wang, Ziying Li, Zhou Cai, Hua Guo, Yaowei Fang, Ran Lin, Wei Liu, Lan Wang, Qiuyu Zheng, Jingyi Xu, You Zhou, Jing Qian, Mingjing Ding, Jieping Luo, Yuanyuan Li, Kai Yang, Dejun Sun, Hongwei Yao, Jianxing He, Wenju Lu
Journal: European Respiratory Journal (2022)

Accumulation of myofibroblasts is critical to fibrogenesis in idiopathic pulmonary fibrosis (IPF). Senescence and insufficient mitophagy in fibroblasts contribute to their differentiation into myofibroblasts, thereby promoting the development of lung fibrosis. Bone morphogenetic protein 4 (BMP4), a multifunctional growth factor, is essential for the early stage of lung development; however, the role of BMP4 in modulating lung fibrosis remains unknown.The aim of this study was to evaluate the role of BMP4 in lung fibrosis using BMP4-haplodeleted mice, BMP4-overexpressed mice, primary lung fibroblasts and lung samples from patients with IPF.BMP4 expression was downregulated in IPF lungs and fibroblasts compared to control individuals, negatively correlated with fibrotic genes, and BMP4 decreased with transforming growth factor (TGF)-β1 stimulation in lung fibroblasts in a time- and dose-dependent manner. In mice challenged with bleomycin, BMP4 haploinsufficiency perpetuated activation of lung myofibroblasts and caused accelerated lung function decline, severe fibrosis and mortality. BMP4 overexpression using adeno-associated virus 9 vectors showed preventative and therapeutic efficacy against lung fibrosis. In vitro, BMP4 attenuated TGF-β1-induced fibroblast-to-myofibroblast differentiation and extracellular matrix (ECM) production by reducing impaired mitophagy and cellular senescence in lung fibroblasts. Pink1 silencing by short-hairpin RNA transfection abolished the ability of BMP4 to reverse the TGF-β1-induced myofibroblast differentiation and ECM production, indicating dependence on Pink1-mediated mitophagy. Moreover, the inhibitory effect of BMP4 on fibroblast activation and differentiation was accompanied with an activation of Smad1/5/9 signalling and suppression of TGF-β1-mediated Smad2/3 signalling in vivo and in vitro.Strategies for enhancing BMP4 signalling may represent an effective treatment for pulmonary fibrosis.
Intra-articular Treatment of Digital Osteoarthritis by Radiosynoviorthesis—Clinical Outcome in Long-term Follow-up
Authors: Hans Ehlich, Ewald Kresnik, Rigobert Klett, Lutz S. Freudenberg, Willm Uwe Kampen
Journal: Clinical Nuclear Medicine (2022)

This retrospective study analyzed the long-term effects of radiosynoviorthesis (RSO) with special emphasis to local joint pain in patients from 4 different RSO centers in Germany and Austria.A total of 168 finger joints in 147 patients with digital joint OA were investigated. The indication for RSO was based on both clinical complaints and a proven synovitis, despite anti-inflammatory pharmacotherapy and previous intra-articular corticosteroid injections. Radiosynoviorthesis was performed according to international guidelines. A numeric visual analog scale (VAS) before and after treatment was used to measure the outcome. Follow-up was done for at least 2 years after treatment, in some patients even over 10 years.Radiosynoviorthesis resulted in a significant reduction of VAS values in most of the patients, lasting for the whole period of follow-up. Two-thirds of the treated joints showed clinically relevant improvement, if a reduction of 30% in VAS values was defined as a reasonable cutoff. The best results were achieved in thumb base joints.This article confirms that RSO is a suitable treatment option for digital joint OA with a proven synovitis. The analgesic effect is long-lasting and comparable to the success of RSO in patients with rheumatoid arthritis.